TUG, Tether containing and UBX domain for GLUT4, is a novel protein that is necessary to sequester GLUT4 away from the plasma membrane during basal states. Upon insulin stimulation the interaction between TUG and GLUT4 is disrupted and GLUT4 is translocated to the plasma membrane where it can transport glucose into the cell. This project will investigate how TUG functions to make glucose available in skeletal muscle. It will provide an understanding of why diabetic patients have impaired glucose uptake and ways to prevent, treat, and cure this disease. Understanding glucose transporter trafficking will provide insight into glucose homeostasis, which is impaired in type 2 diabetes. This study will be useful in developing early prevention strategies for those at risk of developing type 2 diabetes and other metabolic syndromes. In addition, it will help to identify new potential targets for therapeutic agents. It will also explain the molecular mechanism by which exercise may benefit those suffering from diabetes. Ultimately this project will help fight against a growing epidemic. Using cells in culture as well as a transgenic mouse models this study will characterize the role of TUG, AMPK and associated proteins, necessary for normal glucose regulation. By using microscopy, genetic approaches, and protein analysis it will provide an explanation for how glucose uptake becomes impaired. Type 2 diabetes is becoming a global epidemic. While several factors are predictive of diabetes, the molecular basis underlying the onset of the type 2 diabetes is unclear. This study will investigate the underlying factors that lead to the onset of type 2 diabetes.